β淀粉样蛋白1-40和氯化铝双干预阿尔茨海默病大鼠模型的建立

Establishment of a Alzheimer's disease rat model intervened by beta-amyloid protein 1-40 and aluminum chloride

背景:目前已建立的各种阿尔茨海默病动物模型均存在一定的局限性。目的:以β淀粉样蛋白1-40和氯化铝双干预的方式,建立一种较为理想而实用的阿尔茨海默病大鼠模型。方法:健康雄性老年SD大鼠,经Morris水迷宫训练和筛选后,随机分为模型组、生理盐水组和对照组。采用单侧侧脑室一次性注射β淀粉样蛋白1-40和腹腔连续4周隔天注射3%氯化铝的方式建立阿尔茨海默病大鼠模型。以Morris水迷宫实验和跳台实验检测模型大鼠的行为学变化。以刚果红和苏木精-伊红染色检测大鼠海马淀粉样蛋白沉积以及病理学改变。结果与结论:与对照组及生理盐水组相比,模型组大鼠水迷宫实验逃避潜伏期明显延长(P<0.05);跳台实验反应时间、基础错误次数和错误次数显著增加(P<0.05),潜伏期明显缩短(P<0.05)。模型组大鼠海马可见淀粉样蛋白物质沉积,细胞形态发生明显的损伤改变且细胞数量减少。以上结果提示,以β淀粉样蛋白1-40和氯化铝双干预的方式能够成功复制出一种比较理想而实用的阿尔茨海默病大鼠模型。

BACKGROUND：The existed Alzheimer＇s disease（AD） animal models have certain limitations.OBJECTIVE：To establish an ideal and practical AD rat model intervened by β-amyloid protein-40（Aβ1-40） and AlCl3.METHODS：Healthy male aged Sprague Dawley rats were randomly divided into AD model group,saline group and normal control group after Morris water maze training and screening.Rat AD models were established by one-time unilateral intracerebroventricular injection of Aβ1-40 and continuous intraperitoneal injection of AlCl3 every other day for 4 weeks.The behavioral changes of model rats were detected by Morris water maze test and step-down test.The hippocampal amyloid deposition and pathology changes of rats were determined by Congo red and hematoxylin-eosin staining.RESULTS AND CONCLUSIONS：Compared with the normal control group and saline group,the water maze test escape latency of model group rats was significantly longer（P〈0.05）.The reaction time,basal number of errors,and number of errors of step-down test were increased significantly（P〈0.05）.The latency period of step-down test was shortened significantly（P〈0.05）.The amyloid substance deposition,as well as the obvious damage changes in morphology and reduction of cells number could be seen in hippocampus of model group rats.These results suggest that an ideal and practical AD rat model can be successfully established with Aβ1-40 and AlCl3.